Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 455K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flanagan, L. A. Articles by Stossel, T. P. Search for Related Content PubMed PubMed Citation Articles by Flanagan, L. A. Articles by Stossel, T. P. Related Collections Related Article Social Bookmarking                      What's this?

© The Rockefeller University Press, 0021-9525/2001/11/511 $5.00
The Journal of Cell Biology, Volume 155, Number 4, November 12, 2001 511-518

Filamin A, the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cells

Hematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115

Address correspondence to Thomas P. Stossel, Hematology Division, Brigham and Women's Hospital, 221 Longwood Ave., LMRC 301, Boston, MA 02115. Tel.: (617) 278-0380. Fax: (617) 734-2248. E-mail: tstossel{at}rics.bwh.harvard.edu

The Arp2/3 complex and filamin A (FLNa) branch actin filaments. To define the role of these actin-binding proteins in cellular actin architecture, we compared the morphology of FLNa-deficient human melanoma (M2) cells and three stable derivatives of these cells expressing normal FLNa concentrations. All the cell lines contain similar amounts of the Arp2/3 complex. Serum addition causes serum-starved M2 cells to extend flat protrusions transiently; thereafter, the protrusions turn into spherical blebs and the cells do not crawl. The short-lived lamellae of M2 cells contain a dense mat of long actin filaments in contrast to a more three-dimensional orthogonal network of shorter actin filaments in lamellae of identically treated FLNa-expressing cells capable of translational locomotion. FLNa-specific antibodies localize throughout the leading lamellae of these cells at junctions between orthogonally intersecting actin filaments. Arp2/3 complex–specific antibodies stain diffusely and label a few, although not the same, actin filament overlap sites as FLNa antibody. We conclude that FLNa is essential in cells that express it for stabilizing orthogonal actin networks suitable for locomotion. Contrary to some proposals, Arp2/3 complex–mediated branching of actin alone is insufficient for establishing an orthogonal actin organization or maintaining mechanical stability at the leading edge.

Key Words: actin networks; Arp2/3 complex; cell migration; filamins; blebbing

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Battle of the actin junctions

William A. Wells
J. Cell Biol. 2001 155: 494. [Full Text] [PDF]

This article has been cited by other articles:

• Fiori, J. L., Zhu, T.-N., O'Connell, M. P., Hoek, K. S., Indig, F. E., Frank, B. P., Morris, C., Kole, S., Hasskamp, J., Elias, G., Weeraratna, A. T., Bernier, M. (2009). Filamin A Modulates Kinase Activation and Intracellular Trafficking of Epidermal Growth Factor Receptors in Human Melanoma Cells. Endocrinology 150: 2551-2560 [Abstract] [Full Text]  
• Ithychanda, S. S., Das, M., Ma, Y.-Q., Ding, K., Wang, X., Gupta, S., Wu, C., Plow, E. F., Qin, J. (2009). Migfilin, a Molecular Switch in Regulation of Integrin Activation. J. Biol. Chem. 284: 4713-4722 [Abstract] [Full Text]  
• Ferland, R. J., Batiz, L. F., Neal, J., Lian, G., Bundock, E., Lu, J., Hsiao, Y.-C., Diamond, R., Mei, D., Banham, A. H., Brown, P. J., Vanderburg, C. R., Joseph, J., Hecht, J. L., Folkerth, R., Guerrini, R., Walsh, C. A., Rodriguez, E. M., Sheen, V. L. (2009). Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia. Hum Mol Genet 18: 497-516 [Abstract] [Full Text]  
• Zhang, W., Gunst, S. J. (2008). Interactions of Airway Smooth Muscle Cells with Their Tissue Matrix: Implications for Contraction. Proc Am Thorac Soc 5: 32-39 [Abstract] [Full Text]  
• Nakamura, F., Osborn, T. M., Hartemink, C. A., Hartwig, J. H., Stossel, T. P. (2007). Structural basis of filamin A functions. JCB 179: 1011-1025 [Abstract] [Full Text]  
• Millard, T. H., Dawson, J., Machesky, L. M. (2007). Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties. J. Cell Sci. 120: 1663-1672 [Abstract] [Full Text]  
• Stojadinovic, O., Lee, B., Vouthounis, C., Vukelic, S., Pastar, I., Blumenberg, M., Brem, H., Tomic-Canic, M. (2007). Novel Genomic Effects of Glucocorticoids in Epidermal Keratinocytes: INHIBITION OF APOPTOSIS, INTERFERON-{gamma} PATHWAY, AND WOUND HEALING ALONG WITH PROMOTION OF TERMINAL DIFFERENTIATION. J. Biol. Chem. 282: 4021-4034 [Abstract] [Full Text]  
• Tandon, R., Levental, I., Huang, C., Byfield, F. J., Ziembicki, J., Schelling, J. R., Bruggeman, L. A., Sedor, J. R., Janmey, P. A., Miller, R. T. (2007). HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties. Am. J. Physiol. Renal Physiol. 292: F701-F710 [Abstract] [Full Text]  
• Playford, M. P., Lyons, P. D., Sastry, S. K., Schaller, M. D. (2006). Identification of a Filamin Docking Site on PTP-PEST. J. Biol. Chem. 281: 34104-34112 [Abstract] [Full Text]  
• Osmanagic-Myers, S., Gregor, M., Walko, G., Burgstaller, G., Reipert, S., Wiche, G. (2006). Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. JCB 174: 557-568 [Abstract] [Full Text]  
• Nakamura, F., Pudas, R., Heikkinen, O., Permi, P., Kilpelainen, I., Munday, A. D., Hartwig, J. H., Stossel, T. P., Ylanne, J. (2006). The structure of the GPIb-filamin A complex. Blood 107: 1925-1932 [Abstract] [Full Text]  
• Di Nardo, A., Cicchetti, G., Falet, H., Hartwig, J. H., Stossel, T. P., Kwiatkowski, D. J. (2005). Arp2/3 complex-deficient mouse fibroblasts are viable and have normal leading-edge actin structure and function. Proc. Natl. Acad. Sci. USA 102: 16263-16268 [Abstract] [Full Text]  
• Kole, T. P., Tseng, Y., Jiang, I., Katz, J. L., Wirtz, D. (2005). Intracellular Mechanics of Migrating Fibroblasts. Mol. Biol. Cell 16: 328-338 [Abstract] [Full Text]  
• Komano, J., Miyauchi, K., Matsuda, Z., Yamamoto, N. (2004). Inhibiting the Arp2/3 Complex Limits Infection of Both Intracellular Mature Vaccinia Virus and Primate Lentiviruses. Mol. Biol. Cell 15: 5197-5207 [Abstract] [Full Text]  
• Woo, M. S., Ohta, Y., Rabinovitz, I., Stossel, T. P., Blenis, J. (2004). Ribosomal S6 Kinase (RSK) Regulates Phosphorylation of Filamin A on an Important Regulatory Site. Mol. Cell. Biol. 24: 3025-3035 [Abstract] [Full Text]  
• Tseng, Y., An, K. M., Esue, O., Wirtz, D. (2004). The Bimodal Role of Filamin in Controlling the Architecture and Mechanics of F-actin Networks. J. Biol. Chem. 279: 1819-1826 [Abstract] [Full Text]  
• LeClaire, L. L. III, Stewart, M., Roberts, T. M. (2003). A 48 kDa integral membrane phosphoprotein orchestrates the cytoskeletal dynamics that generate amoeboid cell motility in Ascaris sperm. J. Cell Sci. 116: 2655-2663 [Abstract] [Full Text]  
• Le Clainche, C., Pantaloni, D., Carlier, M.-F. (2003). ATP hydrolysis on actin-related protein 2/3 complex causes debranching of dendritic actin arrays. Proc. Natl. Acad. Sci. USA 100: 6337-6342 [Abstract] [Full Text]  
• Takafuta, T., Saeki, M., Fujimoto, T.-T., Fujimura, K., Shapiro, S. S. (2003). A New Member of the LIM Protein Family Binds to Filamin B and Localizes at Stress Fibers. J. Biol. Chem. 278: 12175-12181 [Abstract] [Full Text]  
• Svitkina, T. M., Bulanova, E. A., Chaga, O. Y., Vignjevic, D. M., Kojima, S.-i., Vasiliev, J. M., Borisy, G. G. (2003). Mechanism of filopodia initiation by reorganization of a dendritic network. JCB 160: 409-421 [Abstract] [Full Text]  
• Falet, H., Hoffmeister, K. M., Neujahr, R., Italiano, J. E. Jr., Stossel, T. P., Southwick, F. S., Hartwig, J. H. (2002). Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts. Proc. Natl. Acad. Sci. USA 99: 16782-16787 [Abstract] [Full Text]  
• Medalia, O., Weber, I., Frangakis, A. S., Nicastro, D., Gerisch, G., Baumeister, W. (2002). Macromolecular Architecture in Eukaryotic Cells Visualized by Cryoelectron Tomography. Science 298: 1209-1213 [Abstract] [Full Text]  
• Nakamura, F., Osborn, E., Janmey, P. A., Stossel, T. P. (2002). Comparison of Filamin A-induced Cross-linking and Arp2/3 Complex-mediated Branching on the Mechanics of Actin Filaments. J. Biol. Chem. 277: 9148-9154 [Abstract] [Full Text]  
• Resch, G. P., Goldie, K. N., Krebs, A., Hoenger, A., Small, J. V. (2002). Visualisation of the actin cytoskeleton by cryo-electron microscopy. J. Cell Sci. 115: 1877-1882 [Abstract] [Full Text]  
• Janmey, P. A. (2001). Creating a niche in the cytoskeleton: Actin reorganization by a protein kinase. Proc. Natl. Acad. Sci. USA 98: 14745-14747 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents